Researchers find flawed gene as reason for differences in severity
By Paul Recer
Associated Press
WASHINGTON -- A genetic study in mice suggests that a flawed gene may be the reason the West Nile virus causes a severe, life-threatening illness in some while giving others only a relatively mild infection, according to French researchers.
Scientists at the Pasteur Institute in Paris report this week in the Proceedings of the National Academy of Sciences that a strain of mice carrying a non-working gene are quickly killed by the West Nile virus, while mice with normal genes are not.
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If a similar gene variation is found in humans, it may lead to a new understanding of why only about one in five people infected with the virus develop a serious illness, they said.
American experts said the research is an important step toward finding a drug to treat West Nile, a virus that has caused 11 deaths in the United States this year.
The Centers for Disease Control and Prevention reported Saturday there have been at least 251 human cases of the disease this year.
West Nile is carried by mosquitos whose bite can spread the virus to birds, horses and humans. So far this year, the virus has been found in dead birds, in horses, in humans or in mosquito pools in at least 39 states and the District of Columbia. Human cases have occurred in 11 states and the District of Columbia.
For most people, West Nile causes only flu-like symptoms. But for some patients, particularly the young and the elderly, West Nile can be much more serious, causing a swelling of the brain that can be lethal.
Pasteur Institute scientists, searching for genes that might affect the progression of West Nile infections, tested a series of laboratory mouse strains to see if there is a genetic type that is more likely to die after being exposed to the virus.
They found that animals in the mouse strain called BALB/c all died within 13 days when injected with the West Nile virus. When these animals were mated with other mouse strains, some of the offspring died from the virus, while others were little affected.
By analyzing the genes of both the BALB/c mice and the mixed strains with a high rate of West Nile deaths, the researchers isolated a specific gene variation that increased the susceptibility to the virus, the researchers report. They called the variation the West Nile gene.
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Dr. Jean-Louis Guenet of Pasteur, a co-author of the study, said the West Nile gene allows the virus infection to rage by blocking production of a group of proteins that normally keep viruses from reproducing inside a cell.
"The variation ... stops the action of the gene prematurely, making it nonfunctional," said Guenet. "It is the absence of some proteins made by this gene that leads to susceptibility."
Guenet said the missing proteins participate in a network of proteins that normally degrade viral genes inside a cell.
The exact gene variation has not been found yet in humans, Guenet said, but researchers at the National Institutes of Health said the finding by the Pasteur scientists is important because it moves research closer to finding a drug for West Nile virus.
"The most promising thing about this study is that it could help lead to a drug" that would restore the missing protein and give patients protection against replication of the virus, said Catherine A. Laughlin of the National Institute of Allergy and Infectious Diseases at the NIH.
James M. Meegan, a virology research program leader at NIAID, said the agency is funding research on three West Nile virus vaccines and one may be ready for human trials next year.
Proceedings of the National Academy of Sciences www.pnas.org
West Nile virus: www.cdc.gov/ncidod/dvbid/westnile/
